Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury

Atheroscierosis is a vascular injury characterized by elevated tissue level s of tumor necrosis factor-a (TNF-a), increased expression of endothelial c ell adhesion molecules, and vascular wall inflammatory cell infiltration. F oam cells are associated with atherosclerotic plaque material, and low dens ity lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde ( MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MD A-modified LDL, are present in atherosclerotic human vascular tissue. Aceta ldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to prod uce an antigenically distinct protein adduct, termed the MAA adduct. This s tudy demonstrates that proteins modified in the presence of high concentrat ions of MDA can produce MAA-modified proteins in vitro. In addition, MAA ad ducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-alpha, and cause rHEC upregulation of en dothelial adhesion molecule expression, including ICAM-1. These adhesion mo lecules are required for circulating inflammatory cells to adhere to endoth elium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular t issue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-a lpha concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atheroscle rosis. These data further suggest that previous studies demonstrating MDA m odified protein in atherosclerotic plaque may in fact have MAA modified pro teins associated with them. (C) 1998 Elsevier Science Ireland Ltd. All righ ts reserved.